Multicenter study on the immunogenicity and safety of two recombinant vaccines against hepatitis B

The immunogenicity and safety of a new recombinant hepatitis B vaccine from the Instituto Butantan (Butang®) were evaluated in a multicenter, double-blind, prospective equivalence study in three centers in Brazil. Engerix B® was the standard vaccine. A total of 3937 subjects were recruited and 2754 (70%) met all protocol criteria at the end of the study. All the subjects were considered healthy and denied having received hepatitis B vaccine before the study. Study subjects who adhered to the protocol were newborn infants (566), children 1 to 10 years old (484), adolescents from 11 to 19 years (740), adults from 20 to 30 years (568), and adults from 31 to 40 years (396). Vaccine was administered in three doses on the schedule 0, 1, and 6 months (newborn infants, adolescents, and adults) or 0, 1, and 7 months (children). Vaccine dose was intramuscular 10 µg (infants, children, and adolescents) or 20 µg (adults). Percent seroprotection (assumed when anti-HBs titers were > 10mIU/ml) and geometric mean titer (mIU/ml) were: newborn infants, 93.7% and 351.1 (Butang®) and 97.5% and 1530.6 (Engerix B®); children, 100% and 3600.0 (Butang®) and 97.7% and 2753.1 (Engerix B®); adolescents, 95.1% and 746.3 (Butang®) and 96% and 1284.3 (Engerix B®); adults 20-30 years old, 91.8% and 453.5 (Butang®) and 95.5% and 1369.0 (Engerix B®); and adults 31-40 years old, 79.8% and 122.7 (Butang®) and 92.4% and 686.2 (Engerix B®). There were no severe adverse events following either vaccine. The study concluded that Butang® was equivalent to Engerix B® in children, and less immunogenic but acceptable for use in newborn infants, adolescents, and young adults.

Technological development of 40mg furosemide tablets: equivalence and bioavaibility study in dogs

Furosemide (40mg) was administered to 20 street dogs, 10 males and 10 females, in two different pharmaceutical forms: (1) compressed furosemide 40mg formulated at the Federal University of Pernambuco (UFPE-tablet), and (2) a commercial formulation with equal bioequivalence produced by the Laboratory for Pharmaceutical Technology of Pernambuco State (LAFEPE), the LAFEPE-furosemide. The study aimed to evaluate the kinetics of dissolution of the UFPE-tablet in order to analyze the behavior of bioavailability of the best formulation for veterinary use. The plasmatic concentrations of furosemide for the determination of parameters of pharmacological kinetics were analyzed by high-performance liquid chromatographic method (HPLC). The in vitro study accomplished through physiochemical analyses demonstrated that the formulas of the furosemide tablets attained the pharmaceutical requirements in agreement with USP 23 and the Brazilian Pharmacopoeia. The evaluation accomplished in dogs with UFPE-tablets given in only dose demonstrated uniformity in blood levels indicating stability in maintenance of the pharmaceutical formulation and efficiency in absorption of the active compound. These values are not significantly different in relation to the 5% confidence limit. Regarding maximum concentration (Tmax) time and global bioavaibility assessed by AUC means, there were no considerable differences as well. UFPE-furosemide displayed 743.492µg/mL.h as AUC average value whereas LAFEPE-furosemide had an average of 537.284µg/mL.h.

Bioequivalence Evaluation of Single Doses of Two Tramadol Formulations: A Randomized, Open-Label, Two-Period Crossover Study in Healthy Brazilian Volunteers

Background: Tramadol is a well tolerated and effective analgesic used to treat moderate to severe pain. Several generic formulations of tramadol are available in Brazil; however, published information regarding their bioequivalence in the Brazilian population is not available. A study was designed for Brazilian regulatory authorities to allow marketing of a generic formulation. Objective: The purpose of this study was to compare the bioequivalence of 2 commercial tablet preparations containing tramadol 100 mg marketed for use in Brazil. Methods: A randomized, open-label, 2 x 2 crossover study was performed in healthy Brazilian volunteers under fasting conditions with a washout period of 12 days. Two tablet formulations of tramadol 100 mg (test and reference formulations) were administered as a single oral dose, and blood samples were collected over 24 hours. Tramadol plasma concentrations were quantified using a validated HPLC method. A plasma concentration time profile was generated for each volunteer and then mean values were determined, from which C(max), T(max), AUC(0-t), AUC(0-infinity), k(e), and t(1/2) were calculated using a noncompartmental model. Bioequivalence between the products was determined by calculating 90% CIs for the ratios of C(max), AUC(0-t), and AUC(0-infinity) values for the test and reference products using log-transformed data. Tolerability was assessed by monitoring vital signs (temperature, blood pressure, heart rate), laboratory tests (hematology, blood biochemistry, hepatic function, urinalysis), and interviews with the volunteers before medication administration and every 2 hours during the study. Results: Twenty-six healthy volunteers (13 men, 13 women) were enrolled in and completed the study. Mean (SD) age was 30 (6.8) years (range, 21-44 years), mean weight was 64 (8.3) kg (range, 53-79 kg), and mean height was 166 (6.4) cm (range, 155-178 cm). The 90% CIs for the ratios of C(max) (1.01-1.17), AUC(0-t) (1.00-1.13), and AUC(0-infinity) (1.00-1.14) values for the test and reference products fell within the interval of 0.80 to 1.25 proposed by most regulatory agencies, including the Brazilian regulatory body. No clinically important adverse effects were reported; only mild somnolence was reported by 4 volunteers and mild headaches by 5 volunteers, and there was no need to use medication to treat these symptoms. Conclusion: Pharmacokinetic analysis in these healthy Brazilian volunteers suggested that the test and reference formulations of tramadol 100-mg tablets met the regulatory requirements to assume bio-equivalence based on the Brazilian regulatory definition. (Clin Ther 2010;32:758-765) (C) 2010 Excerpta Medica Inc.

Mild head injury and speed of information processing: A prospective study of professional rugby league players

The sensitivity of several short tests of speed of information processing to the effects of mild head injury in rugby league football was investigated. The measures used were the Symbol Digit Modalities Test, the Digit Symbol Substitution Test, and the Speed of Comprehension Test. Two studies were conducted, the first to examine the effect of practice, the second to determine sensitivity to cognitive impairment immediately following injury. The first study established alternate form equivalence and demonstrated that performance on the Speed of Comprehension and Digit Symbol Substitution tests improved with practice, whereas the Symbol Digit Modalities test remained stable. A second study of 10 players who subsequently sustained mild head injuries showed that measures of speed of information processing were sensitive to impairment in the postacute phase, whereas an untimed task of word recognition (Spot-the-Word) was not. Speed of Comprehension was more sensitive to postinjury impairment than either the Digit Symbol Substitution or Symbol Digit Modalities tests. A repeated baseline assessment before injury using the higher score to reflect a player's potential, allowed measurement of impaired performance on sensitive tests.

A comparative study of telephone versus onsite completion of the WOMAC 3.0 Osteoarthritis Index

Objective. Outcome assessment in clinical trials using the Western Ontario and McMaster University (WOMAC 3.0) Osteoarthritis Index is traditionally achieved through self-administration of the Index. However, in other areas of clinical measurement, telephone administration has been shown to be a reliable method of acquiring data that are both accurate and complete. To address this issue in knee osteoarthritis (OA), we conducted a comparative study of telephone administration by interviewer of WOMAC LK3.0 versus onsite self-completion at the hospital. Methods. Fifty consenting patients with knee OA were randomized to complete the WOMAC LK3.0 Index by telephone interview one day, followed by onsite completion the following day, or vice versa. Neither patients nor interviewers had access to any prior scores. Results. The mean age of the 50 patients was 66.3 years (range 44-82); 34 (68%) were female and 16 (32%) male. There was excellent agreement between the mean office and telephone scores, with mean differences for the WOMAC LK3.0 pain, stiffness, and function subscale scores and total score of 0.09, 0.12, 0.78, and 0.98, respectively. These differences were well within the respective protocol defined equivalence criteria of +/- 1.7, +/- 0.9, +/- 6.4, and +/- 9.1, and represented differences from office scores of 0.9, 2.6, 2.4, and 2.2%, respectively. Conclusion. The use of telephone interviews for the WOMAC LK3.0 Index is a valid method of obtaining OA outcome measurements. These observations have important implications for designing data acquisition strategies for future OA clinical trials and for longterm observational studies.

On the applicability of joint inversion of gravity and resistivity data to the study of a tectonic sedimentary basin in Northern Portugal

The Chaves basin is a pull-apart tectonic depression implanted on granites, schists, and graywackes, and filled with a sedimentary sequence of variable thickness. It is a rather complex structure, as it includes an intricate network of faults and hydrogeological systems. The topography of the basement of the Chaves basin still remains unclear, as no drill hole has ever intersected the bottom of the sediments, and resistivity surveys suffer from severe equivalence issues resulting from the geological setting. In this work, a joint inversion approach of 1D resistivity and gravity data designed for layered environments is used to combine the consistent spatial distribution of the gravity data with the depth sensitivity of the resistivity data. A comparison between the results from the inversion of each data set individually and the results from the joint inversion show that although the joint inversion has more difficulty adjusting to the observed data, it provides more realistic and geologically meaningful models than the ones calculated by the inversion of each data set individually. This work provides a contribution for a better understanding of the Chaves basin, while using the opportunity to study further both the advantages and difficulties comprising the application of the method of joint inversion of gravity and resistivity data.

A questionnaire to evaluate the impact of chronic diseases: validated translation and Illness Effects Questionnaire (IEQ) reliability study

INTRODUCTION: Patients' perception about their health condition, mainly involving chronic diseases, has been investigated in many studies and it has been associated to depression, compliance with the treatment, quality of life and prognosis. The Illness Effects Questionnaire (IEQ) is a tool which makes the standardized evaluation of patients' perception about their illness possible, so that it is brief and accessible to the different clinical settings. This work aims to begin the transcultural adaptation of the IEQ to Brazil through the validated translation and the reliability study. METHODS: The back-translation method and the test-retest reliability study were used in a sample of 30 adult patients under chronic hemodialysis. The reliability indexes were estimated using the Pearson, Spearman, Weighted Kappa and Cronbach's alpha coefficients. RESULTS: The semantic equivalence was reached through the validated translation. In this study, the reliability indexes obtained were respectively: 0.85 and 0.75 (p < 0.001); 0.68 and 0.92 (p < 0.0001). DISCUSSION: The reliability indexes obtained attest to the stability of responses in both evaluations. Additional procedures are necessary for the transcultural adaptation of the IEQ to be complete. CONCLUSION: The results indicate the translation validity and the reliability of the Brazilian version of the IEQ for the sample studied.

Approved Drug Products with Theurapeutic Equivalence Evaluation - 34th edition

The publication, Approved Drug Products with Therapeutic Equivalence Evaluations (the List, commonly known as the Orange Book), identifies drug products approved on the basis of safety and effectiveness by the Food and Drug Administration (FDA) under the Federal Food, Drug, and Cosmetic Act (the Act). Drugs on the market approved only on the basis of safety (covered by the ongoing Drug Efficacy Study Implementation [DESI] review [e.g., Donnatal® Tablets and Librax® Capsules] or pre-1938 drugs [e.g., Phenobarbital Tablets]) are not included in this publication. The main criterion for the inclusion of any product is that the product is the subject of an application with an effective approval that has not been withdrawn for safety or efficacy reasons. Inclusion of products on the List is independent of any current regulatory action through administrative or judicial means against a drug product. In addition, the List contains therapeutic equivalence evaluations for approved multisource prescription drug products. These evaluations have been prepared to serve as public information and advice to state health agencies, prescribers, and pharmacists to promote public education in the area of drug product selection and to foster containment of health care costs. Therapeutic equivalence evaluations in this publication are not official FDA actions affecting the legal status of products under the Act.

The Impact of Instructions on Survey Translation : An Experimental Study

The experimental study described in this paper examined the impact of providing special instructions and supporting material to translators. Specifically, it addressed whether Spanish, Chinese, and French translators provided with explanatory text and guidelines were able to produce translations that were more faithful to the intended meaning of English source survey items, as well as that were more culturally appropriate and natural sounding compared to those of translators who received no such guidance. Study findings indicate that while the provision of special instructions and documentation to translators had a considerable impact on their translations, the direction of the impact (positive or negative) diff ered across the target languages, according to scale ratings of professional survey researchers who were native speakers of those languages.

Equivalence of paper and pencil vs internet forms of the ZKPQ-50-CC in Spanish and French samples

This study was designed to check for the equivalence of the ZKPQ-50-CC (Spanish and French versions) through Internet on-line (OL) and paper and pencil (PP) answer format. Differences in means and devia- tions were significant in some scales, but effect sizes are minimal except for Sociability in the Spanish sample. Alpha reliabilities are also very similar in both versions with no significant differences between formats. A robust factorial structure was found for the two formats and the average congruency coefficients were 0.98. The goodness-of-fit indexes obtained by confirmatory factorial analysis are very similar to those obtained in the ZKPQ-50-CC validation study and they do not differ between the two formats. The multi-group analysis confirms the equivalence among the OL-PP formats in both countries. These results in general support the validity and reliability of the Internet as a method in investigations using the ZKPQ-50-CC.

The career indecision profile : measurement equivalence in two international samples

This study tested for the measurement equivalence of a four-factor measure of career indecision (Career Indecision Profile-65 [CIP-65]) between a U.S. sample and two international samples; one composed of French-speaking young adults from France and Switzerland and the other of Italian ado- lescents. Previous research had supported the four-factor structure of the CIP-65 in both the United States and Iceland but also showed that items on two of the four scales may be interpreted differently by young adults growing up in these two countries. This study extends previous research by testing whether the four CIP-65 factors are measured equivalently in two additional international samples. Results largely supported the configural and metric invariance of the CIP-65 in the United States and international samples, but several scales showed a lack of scalar invariance. Some explanations are offered for these findings along with suggestions for future research and implications for practice.

Asymptotic equivalence between the unconditional maximum likelihood and the square-law nonlinearity symbol timing estimation

This paper provides a systematic approach to theproblem of nondata aided symbol-timing estimation for linearmodulations. The study is performed under the unconditionalmaximum likelihood framework where the carrier-frequencyerror is included as a nuisance parameter in the mathematicalderivation. The second-order moments of the received signal arefound to be the sufficient statistics for the problem at hand and theyallow the provision of a robust performance in the presence of acarrier-frequency error uncertainty. We particularly focus on theexploitation of the cyclostationary property of linear modulations.This enables us to derive simple and closed-form symbol-timingestimators which are found to be based on the well-known squaretiming recovery method by Oerder and Meyr. Finally, we generalizethe OM method to the case of linear modulations withoffset formats. In this case, the square-law nonlinearity is foundto provide not only the symbol-timing but also the carrier-phaseerror.

Effect of the surface charge discretization on electric double layers. A Monte Carlo simulation study

The structure of the electric double layer in contact with discrete and continuously charged planar surfaces is studied within the framework of the primitive model through Monte Carlo simulations. Three different discretization models are considered together with the case of uniform distribution. The effect of discreteness is analyzed in terms of charge density profiles. For point surface groups,a complete equivalence with the situation of uniformly distributed charge is found if profiles are exclusively analyzed as a function of the distance to the charged surface. However, some differences are observed moving parallel to the surface. Significant discrepancies with approaches that do not account for discreteness are reported if charge sites of finite size placed on the surface are considered.

Equivalence and translation strategies in multilingual thesaurus construction

In the present dissertation, multilingual thesauri were approached as cultural products and the focus was twofold: On the empirical level the focus was placed on the translatability of certain British-English social science indexing terms into the Finnish language and culture at a concept, a term and an indexing term level. On the theoretical level the focus was placed on the aim of translation and on the concept of equivalence. In accordance with modern communicative and dynamic translation theories the interest was on the human dimension. The study is qualitative. In this study, equivalence was understood in a similar way to how dynamic, functional equivalence is commonly understood in translation studies. Translating was seen as a decision-making process, where a translator often has different kinds of possibilities to choose in order to fulfil the function of the translation. Accordingly, and as a starting point for the construction of the empirical part, the function of the source text was considered to be the same or similar to the function of the target text, that is, a functional thesaurus both in source and target context. Further, the study approached the challenges of multilingual thesaurus construction from the perspectives of semantics and pragmatics. In semantic analysis the focus was on what the words conventionally mean and in pragmatics on the ‘invisible’ meaning - or how we recognise what is meant even when it is not actually said (or written). Languages and ideas expressed by languages are created mainly in accordance with expressional needs of the surrounding culture and thesauri were considered to reflect several subcultures and consequently the discourses which represent them. The research material consisted of different kinds of potential discourses: dictionaries, database records, and thesauri, Finnish versus British social science researches, Finnish versus British indexers, simulated indexing tasks with five articles and Finnish versus British thesaurus constructors. In practice, the professional background of the two last mentioned groups was rather similar. It became even more clear that all the material types had their own characteristics, although naturally not entirely separate from each other. It is further noteworthy that the different types and origins of research material were not used to represent true comparison pairs, and that the aim of triangulation of methods and material was to gain a holistic view. The general research questions were: 1. Can differences be found between Finnish and British discourses regarding family roles as thesaurus terms, and if so, what kinds of differences and which are the implications for multilingual thesaurus construction? 2. What is the pragmatic indexing term equivalence? The first question studied how the same topic (family roles) was represented in different contexts and by different users, and further focused on how the possible differences were handled in multilingual thesaurus construction. The second question was based on findings of the previous one, and answered to the final question as to what kinds of factors should be considered when defining translation equivalence in multilingual thesaurus construction. The study used multiple cases and several data collection and analysis methods aiming at theoretical replication and complementarity. The empirical material and analysis consisted of focused interviews (with Finnish and British social scientists, thesaurus constructors and indexers), simulated indexing tasks with Finnish and British indexers, semantic component analysis of dictionary definitions and translations, coword analysis and datasets retrieved in databases, and discourse analysis of thesauri. As a terminological starting point a topic and case family roles was selected. The results were clear: 1) It was possible to identify different discourses. There also existed subdiscourses. For example within the group of social scientists the orientation to qualitative versus quantitative research had an impact on the way they reacted to the studied words and discourses, and indexers placed more emphasis on the information seekers whereas thesaurus constructors approached the construction problems from a more material based solution. The differences between the different specialist groups i.e. the social scientists, the indexers and the thesaurus constructors were often greater than between the different geo-cultural groups i.e. Finnish versus British. The differences occurred as a result of different translation aims, diverging expectations for multilingual thesauri and variety of practices. For multilingual thesaurus construction this means severe challenges. The clearly ambiguous concept of multilingual thesaurus as well as different construction and translation strategies should be considered more precisely in order to shed light on focus and equivalence types, which are clearly not self-evident. The research also revealed the close connection between the aims of multilingual thesauri and the pragmatic indexing term equivalence. 2) The pragmatic indexing term equivalence is very much context-depended. Although thesaurus term equivalence is defined and standardised in the field of library and information science (LIS), it is not understood in one established way and the current LIS tools are inadequate to provide enough analytical tools for both constructing and studying different kinds of multilingual thesauri as well as their indexing term equivalence. The tools provided in translation science were more practical and theoretical, and especially the division of different meanings of a word provided a useful tool in analysing the pragmatic equivalence, which often differs from the ideal model represented in thesaurus construction literature. The study thus showed that the variety of different discourses should be acknowledged, there is a need for operationalisation of new types of multilingual thesauri, and the factors influencing pragmatic indexing term equivalence should be discussed more precisely than is traditionally done.